Colorectal cancer is a serious complication in patients with ulcerative colitis or Crohn's disease. Early age at diagnosis, the extent and severity of colonic disease, the presence of primary sclerosing cholangitis, and/or a family history of cancer represent independent risk factors for the development of colorectal cancer. Aspirin has been found to exert chemopreventive effects in colon cancer, but the mechanism by which it exerts these effects may be complex.
One target for activity of chemopreventive drugs against cancers such as colorectal cancer and solid tumor cancers and adenocarcinomas (such as breast, prostate, lung and heptocellular carcinoma) may be improvement of DNA replication. The fidelity of DNA replication is a product of polymerase accuracy, its proofreading activity, and/or the proficiency of the postreplicational mismatch repair system. Inefficiency of fidelity replication can be a key to the development of human cancer. Chemopreventive drugs that increase such efficiency in colorectal cells could significantly reduce the life-threatening manifestations of cancer and diminish cancer deaths.
The overproduction of reactive oxygen species (ROS) is a common underlying mechanism of many pathologies, as they have been shown to damage various cellular components, including proteins, lipids and DNA. Free radicals, especially superoxide (O(2)*−), can be generated in quantities large enough to overwhelm endogenous protective enzyme systems, such as superoxide dismutase (SOD). Overproduction of ROS leads to a prooxidant state also known as oxidative stress. Increased levels of ROS and markers of oxidative stress have been consistently found in such cardiovascular diseases as atherosclerosis or hypertension, and studies involving animal models suggest that antioxidant superoxide dismutase mimetics offer a potential new therapeutic approach to the prevention and treatment of chronic obstructive pulmonary disease as well.
The association between compromised antioxidant status, indices of oxidative damage, and other clinical conditions like diabetes mellitus, cardiac disorders such ischemia, various degenerative disorders (e.g. aging) and hair loss is also well documented. Free radicals such as superoxides have also been implicated in a number of skin conditions including photodamage, general aging of the skin, contact dermatitis, and wrinkling. However, there are limited medications available for treating e.g., oxidative damage.